120042014- Nice Work
1162014- Keep up the good work

9232014- Great job, and nice images

Daren - put these in reverse chronological order also. - DR. B

Week 14 & 15
dtn548_120514_AgaroseGelPCRSquaredTargetsinvert.JPG
Figure 1: (12-5-14) 1kb ladder in well 1 with PCR Squared from the 61 degree Celsius secondary PCR sample in well 2, 3, 4, and 5.

Analysis: Shown in Figure 1, PCR squared was a success by the fact that there were distinct band just below the 1000 DNA sequence band from the ladder. Stp1 is 750 DNA sequence long, so the band are in the correct position. In addition, there is not much contamination of the PCR sample.

Conclusion: Now that PCR squared is successful, future steps in VDS is so proceed with PCR clean up even though the PCR squared sample is not as contaminated at it could have been.

Week 11, 12, 13
dtn548_110414_AgaroseGelPrimaryPCRTargets.JPG
Figure 1: (11-04-14 1pm-5pm): 1kb ladder on well 2 and from well 3-10 there is a temperature gradient from 50.1OC to 58.1OC for secondary PCRdtn548_110414_AgaroseGelSecondaryPCRTargets.JPG
Figure 2: (11-04-14 5pm-8pm) 1kb ladder, primary with 1ul Stacy’s oligo mix, primary with 2ul of Stacy’s oligo mix, and primary with 1ul of Q5 polymerase in well 3, 4, 5 and 6 respectively.

dtn548_110514_AgaroseGelSecondaryPCRTargets.JPG
Figure 3: (11-05-14 4pm-7pm) 1kb ladder in well 2, and from well 3-10 there is a temperature gradient from 50OC to 58OC for primary PCR using Stacy’s oligo mix and the standard components for the sample in the primary PCR protocol
dtn548_111314_AgaroseGelPrimaryPCRTargetsINVERT.JPG
Figure 4: (11-13-14 3:30pm-8pm): 1kb ladder in well 3 with a primary PCR using a 2ul of new oligo mix and 1 ul of Q5 polymerase.
dtn548_111414_AgaroseGelSecondaryPCRTargets.JPG
Figure 5: (11-14-14 10am-1pm): 1kb ladder in well 1, and from well 2-9 there is a temperature gradient from 58OC to 68OC for secondary PCR

Analysis: Within Figure 3, the band was very faint and I had to alter the image in order to see it. To make sure that my secondary worked I ran the procedure again, but with a temperature gradient from 50.1OC to 58.1OC shown in Figure 4. As seen, there were no bands in any of the wells with the secondary PCR sample indicating that the experiment failed. This can be from the fact that my original primary PCR failed and that the smear is from the blue dye. Therefore, that secondary PCR in Figure 3 failed, and that the faint band could have been a leak from my partner’s sample. Due to the fact that my primary PCR did not work, I used Stacy’s oligo mix and altered the produce conveyed in Figure 5. The experiment failed shown by the lack of smears in well 4-6. I decided to do a temperature gradient from 50.1OC to 58. 1OC for the annealing cycle shown in Figure 6, but again the procedure failed. I approached this problem by starting over by making a new oligo mix, and used the standard protocol of primary PCR with the temperatures shown in orange. Shown in Figure 7, there is a definite smear in well 4, so the next step would be to move on to secondary PCR. For my secondary PCR, I used a temperature gradient once again from 58OC to 68OC for the annealing cycle. As shown in Figure 8, some of the wells were a success while some were not by either the bands or lack of bands.

Conclusion: Now that secondary PCR was a success the next step in VDS is to start PCR^2 to amplify even further to use to insert it into the pNIC-Bsa4 vector.


Week 8,9,10Secondary PCR (10-29-14 and 10-30-14)
dtn548_102914_AgaroseGelSecondaryPCRTargets_INVERT.JPG
Figure 1: (10-29-14): 1kb ladder in well 2, primary PCR in well 3, secondary PCR in well 4, primary PCR with 2ul of oligo mix in well 5, secondary PCR from the primary PCR with 2ul of oligo mix in well 6, primary PCR with 1ul of Q5 polymerase in well 7, secondary PCR from the primary PCR with 1ul of Q5 polymerase in well 8. Using regular temperature, and the times in orange in the primary PCR protocol.

dtn548_103014_AgaroseGelSecondaryPCRTargets_INVERT.JPG
Figure 2: (10-30-14) 1kb ladder in well 2, secondary PCR from the primary PCR with 2ul of oligo mix in well 3, secondary PCR from the primary PCR with 1ul of Q5 polymerase in well 4. Using regular temperature, and the times in orange in the primary PCR protocol except added 2 seconds to the annealing cycle. dtn548_103014_AgaroseGelSecondaryPCRTargetsSECONDTRY2.JPG
Figure 3: (10-30-14) 1kb ladder in well 2, secondary PCR from the primary PCR with 2ul of oligo mix in well 3, secondary PCR from the primary PCR with 1ul of Q5 polymerase in well 4. Using regular temperature, and the times in orange in the primary PCR protocol except made the elongation time to 45 seconds.

Analysis: In Figure 1, I used all 3 samples from my primary for secondary PCR, but since there were no solid bands, the experiment failed. For Figure 2, I added two seconds to the annealing time to insure that the primers had enough time to bind to the DNA strand, but once again the experiment failed due to the lack of bands. For Figure 3, I upped the elongation time to 45 seconds so that the Q5 polymerase would have enough time to replicate the DNA.

Conclusion: Now that there is a slight band for secondary PCR, the next step in lab is to start PCR squared into order to amplify the DNA sequence.

Primary PCR (10-13-14 to 10-28-14)
dtn548_101314_AgaroseGelPrimaryPCRTargets.JPG
Figure 1: (10-13-14) 1kb ladder is in well 1 and 10. My primary PCR is in well 8. There is a slight smear, but not compared to the other primary PCR of other students.
dtn548_101414_AgaroseGelPrimaryPCRTargets.JPG
Figure 2: (10-14-14) On well 6 is the 1kb ladder, on well 7 is Jairo’s primary PCR, on well 8 is my secondary PCR, but since there is not a band my experiment failed.
dtn548_101614_AgaroseGelPrimaryPCRTargets.JPG
Figure 3: (10-16-14) 1kb ladder and my primary PCR with a new oligo mix sample in well 1 and 3, respectively.
dtn548_101714_AgaroseGelSecondaryPCRTargets.JPG
Figure 4: (10-17-14) 1kb ladder, primary with 1ul the new oligo mix, primary with 2ul of the new oligo mix, and primary with 1ul of Q5 polymerase in well 2, 3, 4, and 5, respectively.
dtn548_102714_AgaroseGelPrimaryPCRTargets_INVERT.JPG
Figure 7: (10-27-14) 1kb ladder, primary with 1ul jairo’s oligo mix, primary with 2ul of jairo’s oligo mix, and primary with 1ul of Q5 polymerase in well 2, 3, 4, and 5, respectively. dtn548_102814_AgaroseGelPrimaryPCRTargets_INVERT.JPG
Figure 8: (10-28-14) 1kb ladder, primary with 1ul jairo’s oligo mix, primary with 2ul of jairo’s oligo mix, and primary with 1ul of Q5 polymerase in well 2, 3, 4, and 5, respectively.

Analysis: In Figure 1, there was a slight band, so I tried secondary PCR, but as shown in figure 2 in well 8 there is not a band, so the experiment was a failure. Based on the fact that my experiments failure 4 times in a row, I made a new oligo mix just in case if I missed an oligo. In figure 3, the primary failed in well 3. I addressed this failure by making 3 samples: sample 1 with the regular amount of solutions for the primary PCR protocol, sample 2 with 2ul of the new oligo mix, and sample 3 with 1ul of Q5 polymerase. Once again, in Figure 4, there were no smears. Next, I used Jairo’s oligo mix using the same method I used in Figure 4, but as you can see in Figure 5 there were no smears. This failure could have been due to contamination in the agarose gel indicated in from the smug within the 1kb ladder. Therefore, I ran the same experiment from figure 4 and 5, but without contamination within the gel, and there were slight smears in Figure 6.

Conclusion: Now that there are clear smears in Figure 6, the next step in VDS is to conduct secondary PCR.


Week 5, 6, and 7PCR (10-2-14 and 10-3-14)
dtn548_AgaroseGelPrimaryPCR100214.jpg
Figure 1: Trial 1 of Primary PCR will my DNA in well 8.

dtn548_PrimaryPCRgel_10032014.png
Figure 2: Trial 2 of Primary PCR will my DNA in well 4.

Analysis: As shown in Figure 2 and 3, my primary PCR was a failure. In Trail 1, I used the Thermocycler cycling conditions in black, but the reason was probably that I put in the Q5 Polymerase in the sample far sooner than I should. In Trail 2, I used the Thermocycler cycling conditions in orange, but instead of the temperature of 58 Celsius I used a temperature of 62.6 Celsius, which is the melting point.

Conclusion: As both the trail 1 and trail 2 primary PCR failed, the next step is to run another gel to see if it will work.


Midi-Prep (10-2-14)
dtn548_100214_pNicBsa4_Midiprep_Trail1.jpg
Figure 1: Nanodrop trail 1 of pNIC-bsa4 yield

dtn548_100214_pNicBsa4_Midiprep_Trail2.jpg

Figure 2: Nanodrop trail 1 of pNIC-bsa4 yield

Analysis: If all goes well, the pNIC-bsa4 plasmid will be in the last 1.5 mL tube. Some of the DNA may have been stuck in the filter due to the mistake of drawing back the plunger with the filter still attached to the 5mL syringe.

Conclusion: The purpose of this lab is to take the pallet from transformation with pNIC-Bsa4 and clean it so that we will end up with only the plasmid. The average concentration of the finished product is 52.8 ng/uL. Once we have under go transformation and Midi-prep for the DNA of our target protein, the next step would be to insert the target DNA into the pNIC-bsa4 we purified today.


Primer Tail Design (9-29-14)
DNA sequence of STP1
1 ATGGAGATCAGCCTGCTCACTGACATTGGCCAGCGTCGTTCTAACAATCAGGACTTCATC
61 AATCAGTTCGAAAACAAAGCGGGTGTTCCGCTGATCATCCTGGCGGACGGCATGGGCGGT
121 CACCGTGCGGGCAACATCGCTTCCGAAATGACCGTTACCGACCTGGGTTCCGACTGGGCG
181 GAGACCGACTTCTCTGAACTGTCTGAAATTCGTGACTGGATGCTGGTATCTATCGAAACC
241 GAAAACCGTAAAATCTACGAACTCGGTCAATCTGACGACTACAAAGGTATGGGTACCACC
301 ATCGAAGCCGTAGCGATCGTTGGTGACAATATCATCTTCGCGCACGTCGGTGACTCTCGT
361 ATCGGTATCGTTCGTCAAGGTGAATATCACCTGCTGACGAGCGACCACTCTCTGGTTAAC
421 GAACTGGTCAAAGCAGGCCAGCTGACTGAAGAGGAAGCGGCGTCTCACCCGCAGAAAAAC
481 ATCATCACCCAGTCTATCGGTCAGGCGAATCCGGTTGAACCGGACCTCGGTGTACATCTG
541 CTGGAAGAAGGTGACTACCTGGTTGTTAACTCTGACGGTCTGACCAACATGCTGTCTAAC
601 GCGGACATCGCGACCGTTCTGACCCAGGAAAAACCGCTGGACGACAAAAACCAGGACCTG
661 ATCACCCTGGCGAACCATCGTGGTGGTCTGGACAACATCACCGTTGCGCTGGTTTACGTT
721 GAATCTGAAGCGGTAAT
Upstream: TACTTCCAATCCATGGAGATCAGCCTGCTCACTGA
Downstream: CGTTGAATCTGAAGCGGTATAACAGTAAAGGTGGATA
Reverse compliment: TATCCACCTTTACTGTTATACCGCTTCAGATTCAACG
dtn548_092914_ForAndRevPrimers_pNICBsa4.png


Analysis: In order to get the original tail primers to get within 10 of each other I had to reduce the length of the forward tail primer from 35 to 29 nucleotides. One must have the melting temperatures of their tail primers to be closer to each other in order for them to function under the same circumstances. If the melting temperatures of the tail primers are too far apart then there is a possibility that one of the tail primers may denature since the other tail primer’s annealing temperature could be close to the melting temperature of the other.

Conclusion: The purpose of this lab is to design our own primers for pNIC-Bsa4 in order to amplify the production of a certain gene we are trying to get. Once we’ve designed and ordered the tail primers, it will be used in secondary PCR and in PCR squared.


PyMol Refresher (9-19-14)
dtn548_091914_PyMolRefresher_2h2QChainA.png
Fig 1: Chain A of 2H2Q with ionic residues as blue, polar residues as light blue, hydrophobic residues as yellow, and NAP colored by element.
dtn548_091914_PyMolRefresher_2h2QChainB.png
Fig 2: Chain B of 2H2Q with ionic residues as blue, polar residues as light blue, hydrophobic residues as yellow, and NAP colored by element.

dtn548_091914_PyMolRefresher_3CL9.png
Fig 3: 3CL9 with ionic and polar residues as blue, hydrophobic residues as yellow, NAP as cyan, UMP as green, EDO as purple, MTX as red, and the active site as orange.


dtn548_091914_PyMolRefresher_1u72and3cl9.png
Fig 4: 1U72 shown as green lines with its ligands NDP and MTX as red and yellow respectively. 3CL9 shown as cyan lines with its ligands NDP and MTX as blue and pink respectively.

dtn548_091914_PyMolRefresher_3HBB.png
Fig 5: 3HBB with ionic and polar residues as blue, residues as yellow, NAP as red, TMP as green, EDO as purple, MTX as red, and the active site as orange.


Analysis: 1U72 AND 3CL9 are about 50% similar, but this could be due to the fact that 3CL9 has two chains while 1U72 has one. Otherwise, 1U72 and 3CL9 are very similar with there ligands bounded very similarly.

Conclusion: The purpose of this lab is to refresh the students on the procedures of PyMol in order to utilize it when we analyze our target protein. The next step when using pymol is to analyze docking from once virtual screening is finished and determine if ligands bound close enough to know inhibiters to our target protein.

Week 3 and 4


PCR
dtn548_091814_REdigest&PCRgel.png
Figure 1: Agarose Gel of with 1kb lader in lane 2 and 7.

Analysis: As shown on Figure 1 the experiment was a failure. I pipetted at the lowest part off the well and the samples were pushed our, so the gel couldn't capture the DNA sequence.

Conclusion: The next step is to make more of the sample and run the gel again.

Restriction Enzyme Digest
dtn548_091814_REdigest&PCRgel.png
Figure 1: Agarose Gel of with 1kb lader in lane 2 and 7.

Analysis: As shown on Figure 1, the experiment was a failure. This is most likely due to improper calculations; where the amount of ul of plasmid used is wrong. Instead calculations should have been (1,500 ng/ul)/(972.9 np/ul) = 1.5417823ul. Therefore, because there was such a small amount of the pGBR22 protein the EcoRI, PvuII, and EcoRI + PvuII samples were not shown in lanes 4-6.

Conclusion: The next step is to run the gel again with the right amount of pGBR22 to compare the EcoRI, PvuII, and EcoRI + PvuII samples.




Week 1&2
Analyzing DNA Sequence (9-5-15)
dtn548_090514_VDS4_M13R_pGBR22_060509forBB WITH N’s.png
Figure 1: VDS4_M13R_pGBR22_060509forBB.txt WITH N’s
dtn548_090514_VDS4_M13R_pGBR22_060509forBB WITHOUT N’s.png
Figure 2: VDS4_M13R_pGBR22_060509forBB WITHOUT N’s

First BLAST.png
Figure 3: First blast using the VDS4_M13R_pGBR22_060509forBB.txt WITHOUT N’s


Second BLAST.png


Figure 4: Second blast using the VDS4_M13R_pGBR22_060509forBB.txt WITHOUT N’s

dtn548_090514_completedpGBR22sequence.png
Figure 5: completed pGBR22 DNA sequence


Analysis:


Nanodrop (8-29-14)
dtn548_082914_Nanodrop_pGBR22_trial1.jpg
Figure 1: Trail 1 of pGBR22 will a concentration of 257 ng/ul with a maximum absorbance of 5.139 at about 260 nm.
dtn548_082914_Nanodrop_pGBR22_trial2.jpg
Figure 2: Trail 2 of pGBR22 will a concentration of 257 ng/ul with a maximum absorbance of 4.264 at about 260 nm.

Analysis: